This multidisciplinary SCOR proposal continues to focus on the role of the heart in hypertension with emphasis on cellular, biochemical and functional mechanisms whereby the heart participates in pathogenesis of hypertensive cardiovascular disease. The broad objectives of the several proposed studies is to determine the biochemical or neurohumoral mechanisms that underlie the development of hypertensive hypertrophy of the heart and its ultimate fate in congestive heart failure as well as the role the heart and vessels play in the progression of hypertensive disease. This broad objective is carried out in five proposals, four of which focus exclusively on the heart: (1) studies of the mechanisms involved in activation of the myocardial renin angiotensin system and their physiologic relevance to cardiovascular function; (2) studies of calcium regulation in hypertensive hypertrophy; (3) mechanisms whereby stretch or other stimuli are translated into release of ANF from secretory granules in the heart; and (4) the role of the cardiac and peripheral baroreceptors in patients with salt sensitive hypertension and explores further the paradigm in which the heart may play a active role in the modulation of blood pressure levels. Finally, the dissociation between blood pressure control and the development of myocardial hypertrophy is also found in the persistence of peripheral vascular hypertrophy and may be responsible for the deterioration of renal function in patients with renal artery stenosis. This hypothesis was the basis for the prospective randomized study of surgical versus medical treatment of anatomic renal artery stenosis that is being proposed for continuation and completion in this SCOR renewal. From these many studies, at the most basic to the very applied clinical levels, we should substantially further our goals of understanding the pathogenesis of the deleterious effects of arterial hypertension with tangible implications for therapy.